49 articles - From Saturday Feb 26 2022 to Friday Mar 04 2022
Guidelines, position statements, white papers, technical reviews, consensus statements, etc…
meta-analyses and systematic reviews
RCT, clinical trials, retrospective studies, etc…
| Ann Oncol |
Effectiveness of PD-(L)1 Inhibitors Alone or in Combination With Platinum-Doublet Chemotherapy in First-Line (1L) Non-Squamous Non-Small Cell Lung Cancer (nsq-NSCLC) With PD-L1-High Expression Using Real-World Data. Except in the subgroup of never-smoker patients, sparing the chemotherapy in first-line CIT treatment does not appear to impact survival outcomes in Nsq-NSCLC patients with high PD-L1 expression. |
The impact of olaparib dose reduction and treatment interruption on treatment outcome in the SOLO2/ENGOT-ov21 platinum-sensitive recurrent ovarian cancer. Dose reduction and interruption for the management of olaparib associated AE during the first 12 weeks did not impact on PFS and OS. When counselling patients requiring dose reductions or interruptions due to AEs, the results of this study will help assure patients that their outcomes will not be adversely affected. |
| Blood |
A randomized, placebo-controlled, double-blind trial of canakinumab in children and young adults with sickle cell anemia. Post-hoc analysis revealed treatment effects on weight, restricted to pediatric patients. Canakinumab was well tolerated with no treatment-related SAEs and no new safety signal. These findings demonstrate that the inflammation associated with SCA can be reduced by selective IL-1b blockade by canakinumab with potential for therapeutic benefits. |
Age-dependent effects of Igf2bp2 on gene regulation, function, and aging of hematopoietic stem cells in mice. Unexpectedly, Igf2bp2 deficient mice exhibit an amelioration of the aging-associated increase of HSC numbers and myeloid skewed differentiation. Together, Igf2bp2 controls mitochondrial metabolism, protein synthesis, growth, and stemness of young HSC, which is required for full HSC function at young adult age. However, Igf2bp2 gene function is lost during aging and it appears to contribute to HSC aging in two ways: (i) the aging-related loss of Igf2bp2 gene function impairs the growth and repopulation capacity of aging HSC and (ii) the activity of Igf2bp2 at young age contributes to aging-associated HSC expansion and myeloid skewing. |
Anemia in the pediatric patient. The increasing availability of genetic testing is providing new mechanistic insights into inherited anemias and allowing diagnosis in many previously undiagnosed cases. Population-based approaches are being taken to address nutritional anemias. Novel pharmacologic agents and advances in gene therapy-based therapeutics have the potential to ameliorate anemia-associated disease and providing treatment strategies even in the most difficult and complex cases. |
Aryl hydrocarbon receptor-targeted therapy of CD4+ T-cell-mediated idiopathic pneumonia syndrome in mice. Notably, PB502 was by far superior to the endogenous AHR ligand, L-Kynurenine, in promoting the differentiation of both mouse and human FoxP3+ regulatory CD4+ T cells. Our results suggest that the IDO1-AHR axis in lung epithelial cells is associated with IPS repression. A specific AHR agonist may exhibit therapeutic activity against inflammatory and autoimmune diseases by promoting Treg cell differentiation. |
BET-bromodomain and EZH2 inhibitor treated chronic GVHD mice have blunted germinal centers with distinct transcriptomes. Multiple inflammatory and signaling pathways enriched in cGVHD/BO GCBs were reduced by each drug. GCBs from JQ5 but not JQ1 treated mice were enriched for pro-proliferative pathways also seen in GCBs from BM-Only transplanted mice, likely reflecting their underlying biology in the unperturbed state. In conjunction with in vivo data these insights lead us to conclude that epigenetic targeting of the GC is a viable clinical approach for the treatment of cGVHD, and that the EZH2 inhibitor JQ5 and the BET-bromodomain inhibitor JQ1 demonstrated clinical potential for EZH2i and BETi in patients with cGVHD/BO. |
Evidence supporting a role for the immune checkpoint protein B7-H3 in NK cell-mediated cytotoxicity against AML. Epitope mapping studies identified that both T-1A5 and ChT-1A5 antibodies bind to the FG-loop region of B7-H3, which is known to regulate the immunosuppressive function of B7-H3. Furthermore, treatment with ChT-1A5 in combination with human NK cells significantly prolonged survival in AML patient-derived xenograft models. Our results suggest that ChT-1A5 antibody can inhibit the immunosuppressive function of B7-H3 protein as well as induce ADCC in B7-H3+ AML. |
HEATR3 variants impair nuclear import of uL18 (RPL5) and drive Diamond-Blackfan anemia. Consistent with a role of HEATR3 in RP import, HEATR3-depleted cells or patient-derived fibroblasts display reduced nuclear accumulation of uL18. Hematopoietic progenitor cells expressing HEATR3 variants or small-hairpin RNAs knocking down HEATR3 synthesis reveal abnormal acceleration of erythrocyte maturation coupled to severe proliferation defects that are independent of p53 activation. Our study uncovers a new pathophysiological mechanism leading to DBA driven by biallelic HEATR3 variants and the destabilization of a nuclear import protein important for ribosome biogenesis. |
How I Treat with Maintenance Therapy after Allogeneic HCT. Research investigations and clinical applications of this approach have greatly increased in recent years, with an expanding number of available therapeutic agents to introduce in the post-transplant setting. However, many questions and challenges remain regarding the feasibility and clinical impact of maintenance. In this article, we present four common case scenarios addressing select available therapeutic agents as a framework to review published data and ongoing studies and describe our current standard practice in the rapidly evolving field of maintenance therapy after allo-HCT. |
Neutrophil Dysfunction in the Pathogenesis of Cystic Fibrosis. Prominent among PMN defense systems is their ability to generate hypochlorous acid (HOCl), a potent microbicide, by reacting oxidants generated by the NADPH oxidase with myeloperoxidase (MPO) released from azurophilic granules in the presence of chloride (Cl-). Products of the MPO-H2O2-Cl system oxidize susceptible biomolecules and support a robust antimicrobial action against many, but not all, potential human pathogens. Underscoring that the MPO-H2O2-Cl system is integral to optimal host defense and proper regulation of inflammation, individuals with defects in any component of this system, as seen in chronic granulomatous disease or MPO deficiency, incur increased rates or severity of infection and signs of dysregulated inflammatory responses. |
SUMOylation inhibitor subasumstat potentiates rituximab activity by IFN1-dependent macrophage and NK cell stimulation. In vivo studies demonstrated enhanced antitumor activity of TAK-981 and rituximab in CD20-positive lymphoma xenograft models. Combination of TAK-981 with anti-CD38 antibody daratumumab also resulted in enhanced antitumor activity. TAK-981 is currently being studied in phase 1 clinical trials (NCT03648372, NCT04074330, NCT04776018, and NCT04381650) for the treatment of patients with lymphomas and solid tumors. |
| Blood Adv |
Contact and intrinsic coagulation pathways are activated and associated with adverse clinical outcomes in COVID-19. Among the protease:serpin complexes measured, FIXa:AT complexes were uniquely associated with clinical indices of disease severity, specifically the total length of hospitalization, length of ICU stay, and extent of lung CT changes. We conclude that the contact/intrinsic pathway may contribute to the pathogenesis of the prothrombotic state in COVID-19. Larger prospective studies are required to confirm whether FIXa:AT complexes are a clinically useful biomarker of adverse clinical outcomes. |
Prediction of outcomes after second-line treatment for acute graft-versus-host disease. Predictive models for both endpoints included the serum albumin and total bilirubin concentrations at the onset of second-line treatment, patient age at onset of second-line therapy, plus a combination of abdominal pain/stage-4 gut involvement. Optimism-corrected areas under the receiver-operator characteristic curve and Brier scores were 77.4 and 0.169 for 6-month mortality, respectively, and 80.0 and 0.169 for 12-month mortality. We identify risk factors associated with mortality and failure after second-line treatment of acute GVHD, provide historical benchmarks for assessment of FFS and OS in other studies, and propose predictive models for 6- and 12-month mortality that could be used to generate population-specific benchmarks. |
The T Moreover, we identified high-confidence TAp63 binding regions in genes mainly implicated in immune response and DNA-damage procedures. Finally, we found that up-regulated TAp63 expression levels render CLL cells less responsive to apoptosis induction with the BCL2 inhibitor, venetoclax. On these grounds, TAp63 appears to act as a positive modulator of BCL2, hence contributing to the anti-apoptotic phenotype that underlies clinical aggressiveness and treatment resistance in CLL. |
Utility of PET/CT in Assessing Early Treatment Response in Patients With Newly Diagnosed Multiple Myeloma. We then examined the additive value of PET/CT on the hematologic response achieved at 6 months, and we found that PET/CT (-) is associated with significantly increased median TTNT and OS for both the very good partial response (VGPR) group and the less than VGPR group. Importantly, PET/CT retained prognostic significance after adjusting for multiple other predictive variables. We conclude that a PET/CT (-) at 6 months confers a significant prognostic advantage for newly diagnosed MM patients and adds significant value to the hematologic response assessment. |
| Blood Cancer J |
CD19-targeted BiTE expression by an oncolytic vaccinia virus significantly augments therapeutic efficacy against B-cell lymphoma. In vivo study showed that OVV-CD19BiTE selectively replicated within tumor tissue, and contributed to a more significantly increased percentage of CD3, CD8, and naïve CD8 T subpopulations within tumors in contrast to blinatumomab. More importantly, treatment with OVV-CD19BiTE both in vitro and in vivo resulted in potent antitumor activity in comparison with control OVV or blinatumomab, a first-in-class BiTE, thereby resulting in long-term tumor remissions without relapse. The study provides strong evidence for the therapeutic benefits of CD19-targeting BiTE expression by OVV, and suggests the feasibility of testing the approach in clinical trials. |
| Haematologica |
How I diagnose and treat chronic myelomonocytic leukemia. Patients with pCMML have a more aggressive course with higher rates of AML transformation. Allogeneic stem cell transplant remains the only potential cure for CMML, however, given the advanced median age at presentation (73 years) and comorbidities, is an option to only a few affected patients (10%). While DNA methyltransferase inhibitors are approved for the management of CMML, the overall response rates are 40-50%, with true complete remission rates of. |
Rituximab in addition to LMB-based chemotherapy regimen in children and adolescents with primary mediastinal large B-cell lymphoma: results of the French LMB2001 prospective study. Only 1/21 patients treated with rituximab and LMB-based chemotherapy had local early treatment failure but achieved prolonged complete remission with second-line chemotherapy and radiotherapy. Intensive LMB-based chemotherapy with rituximab achieved excellent survival in children/adolescents with PMLBL. Further international prospective studies are required to confirm these results in this population. |
Plenty of the editorials are available as full text through the publisher website using the provided link
| Am J Hematol |
Current Approaches to Management of Newly Diagnosed Multiple Myeloma. For induction therapy prior to ASCT, A proteasome inhibitor-IMiD combination remains standard with monoclonal antibody-based quadruplets preferred in high-risk patients. Among transplant ineligible patients, those with standard risk MM should receive DRd continued until disease progression, while bortezomib containing regimens (VRd or VRd lite) can be considered for high-risk patients. Finally, standard risk patients should receive lenalidomide maintenance after induction/ASCT, while a proteasome inhibitor-IMiD combinations should be used for high risk patients. |
| Blood |
| J Hematol Oncol |
The long and short non-coding RNAs modulating EZH2 signaling in cancer. Furthermore, lncRNAs induce EZH2 by modulating miRNA expression. Circular RNAs (CircRNAs), like lncRNAs, affect EZH2 expression via targeting miRNAs. These areas are discussed in the present review with a focus on molecular pathways leading to clinical translation. |
Letters to the editors and authors’ replies
| Ann Oncol |
all remaining publications eg case reports, images of the month, etc…
| Blood |
| Blood Adv |
| Haematologica |
| Leukemia |